Oral Care Compositions and Methods of Using the Compositions

ABSTRACT

An oral care composition comprising zinc phosphate and stannous fluoride.

BACKGROUND

Dental erosion involves demineralization and damage to the toothstructure due to acid attack from nonbacterial sources. Erosion is foundinitially in the enamel and, if unchecked, may proceed to the underlyingdentin. Dental erosion may be caused or exacerbated by acidic foods anddrinks, exposure to chlorinated swimming pool water, and regurgitationof gastric acids.

The tooth enamel is a negatively charged surface, which naturally tendsto attract positively charged ions such as hydrogen and calcium ions,while resisting negatively charged ions such as fluoride ions. Dependingupon relative pH of surrounding saliva, the tooth enamel will lose orgain positively charged ions such as calcium ions. Generally saliva hasa pH between 7.2 and 7.4. When the pH is lowered the fluid mediumsurrounding the tooth becomes undersaturated with respect to the toothmineral phase and the tooth dissolves, releasing calcium and phosphateions. This damages the enamel and creates a porous, sponge-likeroughened surface. If saliva remains acidic over an extended period,then remineralization may not occur, and the tooth will continue to loseminerals, causing the tooth to weaken and ultimately to lose structure.

Heavy metal ions, such as zinc, are resistant to acid attack. Zinc ranksabove hydrogen in the electrochemical series, so that metallic zinc inan acidic solution will react to liberate hydrogen gas as the zincpasses into solution to form di-cations, Zn²⁺. Zinc has also been shownto have anti-microbial properties in plaque and caries studies.

Soluble zinc salts, such as zinc citrate, have been used in dentifricecompositions, but have several disadvantages. Zinc ions in solutionimpart an unpleasant, astringent mouthfeel, so formulations that provideeffective levels of zinc, and also have acceptable organolepticproperties, have been difficult to achieve. Moreover, free zinc ions mayreact with fluoride ions to produce zinc fluoride, which is insolubleand so reduces the availability of both the zinc and the fluoride.Finally, the zinc ions will react with anionic surfactants such assodium lauryl sulfate, thus interfering with foaming and cleaning.

Zinc phosphate (Zn₃(PO₄)₂) is insoluble in water, although soluble inacidic or basic solutions, e.g., solutions of mineral acids, aceticacid, ammonia, or alkali hydroxides. See, e.g., Merck Index, 13^(th) Ed.(2001) p. 1812, monograph number 10205. Partly because it is viewed inthe art as a generally inert material, zinc phosphate is commonly usedin dental cements, for example in cementation of inlays, crowns,bridges, and orthodontic appliances, which are intended to endure in themouth for many years. Zinc phosphate dental cements are generallyprepared by mixing zinc oxide and magnesium oxide powders with a liquidconsisting principally of phosphoric acid, water, and buffers, so thecement comprising zinc phosphate is formed in situ by reaction withphosphoric acid.

Stannous fluoride is well known for use in clinical dentistry with ahistory of therapeutic benefits over forty years. However, untilrecently, its popularity has been limited by its instability in aqueoussolutions. The instability of stannous fluoride in water is primarilydue to the reactivity of the stannous ion (Sn²⁺). Tin readily hydrolysesabove a pH of 4, resulting in precipitation from solution, with aconsequent loss of the therapeutic properties.

Approaches to overcoming the stability problem with stannous fluorideinclude forming a gel in no or very low water formulations by dissolvingstannous fluoride in an anhydrous material such as glycerin, or by usinga chelating agent. However, these can be relatively expensive andtedious solutions.

There is a desire for improved compositions for treating and reducingerosion of tooth enamel. There is also a desire for novel anti-microbialcompositions that are stable in water and relatively simple tomanufacture.

BRIEF SUMMARY

An embodiment of the present disclosure is directed to an oral carecomposition comprising zinc phosphate and stannous fluoride. In someembodiments, the zinc phosphate is added to the dentifrice as apreformed salt.

Further areas of applicability of the present disclosure will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the disclosure, are intended forpurposes of illustration only and are not intended to limit the scope ofthe disclosure.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the disclosure,its application, or uses.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight. The amounts given are based on the active weightof the material.

An embodiment of the present disclosure is directed to an oral carecomposition for intermittent use, e.g., daily use, in the form of adentifrice, gel, lozenge, mint, chewing gum or other suitable oral careformulation. The oral care composition comprises zinc phosphate,stannous fluoride and water. In some embodiments, the zinc phosphate isadded to the oral care composition as a preformed salt. As used herein,the term “preformed salt”—when used in reference to zinc phosphate—meansthat the zinc phosphate is not formed in situ in the oral carecomposition, e.g., through the reaction of phosphoric acid and anotherzinc salt.

In one aspect, the present disclosure therefore provides an oral carecomposition (Composition 1) comprising an orally acceptable carrier,zinc phosphate and stannous fluoride. In further embodiments of thisaspect, the present disclosure provides:

-   -   1.1 Composition 1, wherein the zinc phosphate is a preformed        salt of zinc phosphate.    -   1.2 Composition 1 or 1.2, wherein the zinc phosphate is present        in an amount sufficient so that the stannous fluoride        dissociates to provide a therapeutically effective amount of        stannous ions in aqueous solution.    -   1.3 Any preceding composition, wherein the amount of zinc        phosphate is from 0.05 to 5% by weight, relative to the weight        of the oral care composition, for example, from 0.1 to 4% by        weight, or from 0.5 to 3% by weight, or from 0.5 to 2% by        weight, or from 0.8 to 1.5% by weight, or from 0.9 to 1.1% by        weight, or about 1% by weight, or from 2 to 3% by weight, or        about 2%, or about 2.25% or about 2.5%, by weight.    -   1.4 Any preceding composition, wherein the amount of the        stannous fluoride is from 0.05% to 11% by weight, relative to        the weight of the oral care composition, for example, from 0.05        to 7% by weight, or from 0.1% to 5% by weight, or from 0.2 to 3%        by weight, or from 0.2 to 2% by weight, or from 0.2 to 1% by        weight, or from 0.2 to 0.8% by weight, or from 0.4 to 0.6% by        weight, or from 0.4 to 0.5% by weight, or about 0.45% by weight        (e.g., 0.454%).    -   1.5 Any preceding composition, wherein the amount of the water        is about 12% by weight or more, relative to the weight of the        oral care composition, for example, from 15% to 85%, or from 20%        to 75%, or from 20% to 40% or from 20% to 30%, or from 25% to        50%, or from 30% to 40%, for example, about 35%, or about 25% or        about 20%.    -   1.6 Any preceding composition, wherein the oral care composition        further comprises an abrasive, for example, silica abrasives,        calcium abrasives, and other abrasives as disclosed herein.    -   1.7 Any preceding composition, further comprising one or more        humectants and/or one or more surfactants, as described herein.    -   1.8 Any preceding composition, further comprising an effective        amount of one or more alkali phosphate salts for example        orthophosphates, pyrophosphates, tripolyphosphates,        tetraphosphates or higher polyphosphates.    -   1.9 Composition 1.8, wherein the alkali phosphate salts comprise        tetrasodium pyrophosphate or tetrapotassium pyrophosphate, for        example, in an amount of 0.5 to 5% by weight of the composition,        e.g., 1-3%, or 1-2% or about 2% by weight, or about 2-4%, or        about 3-4% or about 4% by weight of the composition.    -   1.10 Composition 1.8 or 1.9, wherein the alkali phosphate salts        comprise sodium tripolyphosphate or potassium tripolyphosphate,        for example, in an amount of 0.5 to 6% by weight of the        composition, e.g., 1-4%, or 2-3% or about 3% by weight.    -   1.11 Any preceding composition, further comprising a whitening        agent.    -   1.12 Any preceding composition, further comprising one or more        sources of zinc ions in addition to the zinc phosphate, for        example a zinc salt selected from zinc citrate, zinc oxide, zinc        lactate, zinc pyrophosphate, zinc sulfate, or zinc chloride.    -   1.13 Any preceding composition, wherein the oral care        composition is a dentifrice.    -   1.14 Any preceding composition, wherein the composition        comprises        -   from 0.5 to 3% by weight zinc phosphate;        -   from 0.05 to 11% by weight stannous fluoride;        -   from 1 to 8% by weight alkali phosphate salts selected from            sodium phosphate dibasic, potassium phosphate dibasic,            dicalcium phosphate dihydrate, tetrasodium pyrophosphate,            tetrapotassium pyrophosphate, calcium pyrophosphate, sodium            tripolyphosphate, and mixtures of any two or more of these,            relative to the weight of the oral care composition; and        -   a silica abrasive.    -   1.15 Any preceding composition, wherein the composition is        essentially free of a halogenated diphenyl ether.    -   1.16 Any preceding composition, wherein the oral care        composition is a dentifrice (e.g., a toothpaste or oral gel),        powder (e.g., tooth powder), cream, strip or gum (e.g., chewing        gum), for example, wherein the oral care composition is a gel.    -   1.17 Any preceding composition, wherein the oral care        composition is a lozenge or mint.    -   1.18 Any preceding composition, wherein the oral care        composition is a chewing gum.    -   1.19 Any preceding composition, wherein the pH of the        composition is from 6 to 9, such as from 6.5 to 8, or from 3 to        7 or from 4 to 7 or from 5 to 7, or from 5 to 6.    -   1.20 Any preceding composition, wherein the composition is a        single-phase composition (e.g., not a dual-phase composition).    -   1.21 Any preceding composition, wherein the composition does not        comprise one or more of zinc oxide, zinc citrate, or zinc        lactate.    -   1.22 Any preceding composition, wherein the zinc phosphate is        the only zinc ion source.    -   1.23 Any preceding composition, wherein the composition is        essentially free of hexametaphosphate salts (e.g., sodium        hexametaphosphate).

Any amount of zinc phosphate that is effective for protecting againstenamel erosion and/or providing any of the other benefits describedherein can be employed. Examples of suitable amounts of zinc phosphatecan range from 0.05 to 5% by weight, such as from 0.1 to 4% by weight,or from 0.5 to 3% by weight, or from 0.5 to 2% by weight, or from 0.8 to1.5% by weight, or from 0.9 to 1.1% by weight, or about 1% by weight,relative to the weight of the oral care composition.

While zinc phosphate is considered insoluble (e.g., poorly soluble), inwater, when placed in formulation, e.g., at acidic or basic pH, zincphosphate can dissolve sufficiently upon use to provide an effectiveconcentration of zinc ions to the enamel, thereby protecting againsterosion, reducing bacterial colonization and biofilm development, andproviding enhanced shine to the teeth. It has also been discovered thatzinc phosphate in a formulation with a second phosphate source enhancesphosphate deposition. As explained in WO2014/088573, the disclosure ofwhich is hereby incorporated by reference in its entirety, this is allunexpected, in view of the poor solubility of zinc phosphate, and theart-recognized view that it is substantially inert in conditions in theoral cavity, as evidenced by its widespread use in dental cement. At thesame time, the formulations containing zinc phosphate do not exhibit thepoor taste and mouthfeel, poor fluoride delivery, and poor foaming andcleaning associated with conventional zinc-based oral care products,which use more soluble zinc salts.

An amount of stannous fluoride, preferably an effective amount, isemployed in combination with the zinc phosphate in the compositions ofthe present disclosure. For example, the stannous fluoride can beemployed in an amount that is effective for providing anti-microbialbenefits, such as anti-caries protection and/or anti-gingivitisprotection, and/or anti-erosion benefits for protection of tooth enamel.Examples of suitable amounts of stannous fluoride range from 0.05% byweight to 11% by weight, such as from 0.05 to 7% by weight, or from 0.1%to 5% by weight, or from 0.2 to 3% by weight, or from 0.2 to 2% byweight, or from 0.2 to 1% by weight, or from 0.2 to 0.8% by weight, orfrom 0.4 to 0.6% by weight, or from 0.4 to 0.5% by weight, or about0.45% by weight (e.g., 0.454%), relative to the total weight of thedentifrice composition. Formulations can include stannous levels,provided by stannous fluoride, ranging for example, from 3,000 ppm to15,000 ppm (mass fraction) stannous ions in the total composition. Inembodiments, the soluble stannous content can range from 0.1 wt % to 0.5wt %, or more, such as from 0.15 wt % to 0.32 wt %, based on the totalweight of the composition.

The combination of zinc and stannous ions provides one or more of thefollowing benefits: improved antimicrobial benefits compared to the zincions alone; improved control of plaque and/or gingivitis; improvedprotection against the erosion of tooth enamel.

In compositions comprising significant amounts of water, the zincphosphate acts as a stabilizing agent for the stannous fluoride, so thatthe stannous fluoride remains in solution in the water. As discussedabove, stannous fluoride is generally considered unstable in water dueto the hydrolytic and oxidative loss of stannous ions at typical pHranges employed in oral care compositions. Consequently, stannousfluoride is generally employed in compositions containing no water orlow water, or with a chelating agent. Tedious procedures are employed inorder to provide stable solutions in which the tendency of the stannousion to be oxidized or hydrolyzed is inhibited. Applicants havesurprisingly found that zinc phosphate and stannous fluoride can becombined together in a single phase formulation using standard mixingprocesses and typical pH ranges to form stable aqueous oral carecompositions. The zinc phosphate remains essentially insoluble in thecomposition. However, the stannous fluoride has been shown to remainsoluble and stable in solutions comprising relatively high amounts ofwater for extended periods of time, such as 3 months or longer at 40° C.Under typical storage conditions, the stannous fluoride is expected toremain sufficiently stable to provide a desired shelf life of, forexample, 1 to 2 years or longer.

Any desired amount of water can be employed in the compositions of thepresent disclosure. Examples of suitable amounts of water range from 12%by weight or more, such as from 15% to 98 or 99% by weight. For example,the amount of water may be from 15% to 85%, or from 20% to 75%, or from25% to 50%, or from 30% to 40%, for example, about 35%, by weight of thecomposition. Amounts will vary depending on the type of oral carecomposition. In an embodiment where the composition is a dentifrice,such as toothpaste, the amount of water can range, for example, from 15%to 60% by weight, such as from 25% to 50%, or from 25% to 40% by weight,relative to the total weight of the dentifrice composition.

The amount of water in the compositions as set forth in the above rangesincludes both free water which is added separately plus that amount thatis introduced with the other ingredients. Water employed in thepreparation of the oral compositions of the present disclosure can bedeionized (sometimes referred to as demineralized water) and/or free oforganic impurities. Sources of water beyond the directly added waterinclude ingredients which are commonly add as aqueous solutions, such assorbitol (commonly provided as a 70% w/w aqueous solution).

The compositions may optionally comprise additional ingredients suitablefor use in oral care compositions. Examples of such ingredients includeactive agents, such as a fluoride source and/or a phosphate source inaddition to zinc phosphate. The compositions may be formulated in asuitable dentifrice base, e.g., comprising abrasives, e.g., silicaabrasives, surfactants, foaming agents, vitamins, polymers, enzymes,humectants, thickeners, additional antimicrobial agents, preservatives,flavorings, colorings, and/or combinations thereof. Examples of suitabledentifrice bases are known in the art. Alternatively, the compositionsmay be formulated as a gel (e.g., for use in a tray), chewing gum,lozenge or mint. Examples of suitable additional ingredients that can beemployed in the compositions of the present disclosure are discussed inmore detail below.

Active Agents: The compositions of the disclosure may comprise variousother agents that are active to protect and enhance the strength andintegrity of the enamel and tooth structure and/or to reduce bacteriaand associated tooth decay and/or gum disease or to provide otherdesired benefits. Effective concentration of the active ingredients usedherein will depend on the particular agent and the delivery system used.The concentration will also depend on the exact salt or polymerselected. For example, where the active agent is provided in salt form,the counterion will affect the weight of the salt, so that if thecounterion is heavier, more salt by weight will be required to providethe same concentration of active ion in the final product.

Compositions of the disclosure may contain from 0.1 to 1 wt % of anantibacterial agent, such as about 0.3 wt. %. Any suitable antimicrobialactives can be employed.

Fluoride Ion Source: The oral care compositions can include one or moreadditional fluoride ion sources, e.g., soluble fluoride salts. A widevariety of fluoride ion-yielding materials can be employed as sources ofsoluble fluoride in the present compositions. Examples of suitablefluoride ion-yielding materials are found in U.S. Pat. No. 3,535,421, toBriner et al.; U.S. Pat. No. 4,885,155, to Parran, Jr. et al. and U.S.Pat. No. 3,678,154, to Widder et al, the disclosure of each of which ishereby incorporated by reference in their entirety. Representativefluoride ion sources include, but are not limited to, sodium fluoride,potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate,ammonium fluorosilicate, amine fluoride, ammonium fluoride, andcombinations thereof. In certain embodiments the fluoride ion sourceincludes sodium fluoride, sodium monofluorophosphate as well as mixturesthereof. In certain embodiments, the oral care composition of thedisclosure may contain stannous fluoride and any additional source offluoride ions or fluorine-providing agents in amounts sufficient tosupply, in total, from 25 ppm to 25,000 ppm (mass fraction) of fluorideions, generally at least 500 ppm, e.g., from 500 to 2000 ppm, e.g., from1000 to 1600 ppm, e.g., about 1450 ppm. The appropriate level offluoride will depend on the particular application. A toothpaste forgeneral consumer use would typically have from 1000 to about 1500 ppm,with pediatric toothpaste having somewhat less. A dentifrice or coatingfor professional application could have as much as 5,000 or even about25,000 ppm fluoride. Additional fluoride ion sources may be added to thecompositions of the disclosure at a level of from 0.01 wt. % to 10 wt. %in one embodiment or from 0.03 wt. % to 5 wt. %, and in anotherembodiment from 0.1 wt. % to 1 wt. % by weight of the composition. Asdiscussed above, weights of fluoride salts to provide the appropriatelevel of fluoride ion will vary based on the weight of the counterion inthe salt.

Abrasives: The compositions of the disclosure can include abrasives.Examples of suitable abrasives include silica abrasives, such asstandard cleaning silicas, high cleaning silicas or any other suitableabrasive silicas. Additional examples of abrasives that can be used inaddition to or in place of the silica abrasives include, for example, acalcium phosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂),hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate(CaHPO₄.2H₂O, also sometimes referred to herein as DiCal) or calciumpyrophosphate; calcium carbonate abrasive; or abrasives such as sodiummetaphosphate, potassium metaphosphate, aluminum silicate, calcinedalumina, bentonite or other siliceous materials, or combinationsthereof.

Silica abrasive polishing materials useful herein, as well as the otherabrasives, generally have an average particle size ranging between 0.1and 30 microns, such as between 5 and 15 microns. The silica abrasivescan be from precipitated silica or silica gels, such as the silicaxerogels described in U.S. Pat. No. 3,538,230, to Pader et al. and U.S.Pat. No. 3,862,307, to Digiulio, the disclosures of which areincorporated herein by reference in their entireties. Particular silicaxerogels are marketed under the trade name Syloid® by the W. R. Grace &Co., Davison Chemical Division. The precipitated silica materialsinclude those marketed by the J. M. Huber Corp. under the trade nameZeodent®, including the silica carrying the designation Zeodent 115 and119. These silica abrasives are described in U.S. Pat. No. 4,340,583, toWason, the disclosure of which is incorporated herein by reference inits entirety. In certain embodiments, abrasive materials useful in thepractice of the oral care compositions in accordance with the disclosureinclude silica gels and precipitated amorphous silica having an oilabsorption value of less than 100 cc/100 g silica, such as from 45cc/100 g to 70 cc/100 g silica. Oil absorption values are measured usingthe ASTA Rub-Out Method D281. In certain embodiments, the silicas arecolloidal particles having an average particle size of from 3 microns to12 microns, and from 5 to 10 microns. Examples of low oil absorptionsilica abrasives useful in the practice of the disclosure are marketedunder the trade designation Sylodent XWA® by Davison Chemical Divisionof W.R. Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silicahydrogel composed of particles of colloidal silica having a watercontent of 29% by weight averaging from 7 to 10 microns in diameter, andan oil absorption of less than 70 cc/100 g of silica is an example of alow oil absorption silica abrasive useful in the practice of the presentdisclosure.

Any suitable amount of silica abrasive can be employed. Examples ofsuitable amounts include 10 wt. % or more dry weight of silicaparticles, such as from 15 wt. % to 30 wt. % or from 15 wt. % to 25 wt.%, based on the total weight of the composition.

Foaming agents: The oral care compositions of the disclosure also mayinclude an agent to increase the amount of foam that is produced whenthe oral cavity is brushed. Illustrative examples of agents thatincrease the amount of foam include, but are not limited topolyoxyethylene and certain polymers including, but not limited to,alginate polymers. The polyoxyethylene may increase the amount of foamand the thickness of the foam generated by the oral care compositions ofthe present disclosure. Polyoxyethylene is also commonly known aspolyethylene glycol (“PEG”) or polyethylene oxide. The polyoxyethylenessuitable for compositions of the present disclosure may have a molecularweight of from 200,000 to 7,000,000. In one embodiment the molecularweight may be from 600,000 to 2,000,000 and in another embodiment from800,000 to 1,000,000. Polyox® is the trade name for the high molecularweight polyoxyethylene produced by Union Carbide. The foaming agent,(e.g., polyoxyethylene) may be present in an amount of from 0.1% to 50%,in one embodiment from 0.5% to 20% and in another embodiment from 1% to10%, or from 2% to 5% by weight of the oral care compositions of thepresent disclosure.

Surfactants: The compositions useful in the compositions of the presentdisclosure may contain anionic surfactants, for example:

-   -   i. water-soluble salts of higher fatty acid monoglyceride        monosulfates, such as the sodium salt of the monosulfated        monoglyceride of hydrogenated coconut oil fatty acids such as        sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride        sulfate,    -   ii. higher alkyl sulfates, such as sodium lauryl sulfate,    -   iii. higher alkyl-ether sulfates, e.g., of formula        CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10,        n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium        laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na),    -   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene        sulfonate (sodium lauryl benzene sulfonate),    -   v. higher alkyl sulfoacetates, such as sodium lauryl        sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid        esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate        (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl        sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In certain embodiments,the anionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having from 10 to 18 carbon atoms in the alkyl radicaland the water-soluble salts of sulfonated monoglycerides of fatty acidshaving from 10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroylsarcosinate and sodium coconut monoglyceride sulfonates are examples ofanionic surfactants of this type. In particular embodiments, the anionicsurfactant is selected from sodium lauryl sulfate and sodium etherlauryl sulfate. In a particular embodiment, the compositions of thedisclosure comprise sodium lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. In one embodiment,the anionic surfactant is present in a toothpaste at from 0.3% to 4.5%by weight, e.g., about 1.5%. The compositions of the disclosure mayoptionally contain mixtures of surfactants, e.g., comprising anionicsurfactants and other surfactants that may be anionic, cationic,zwitterionic or nonionic. Generally, suitable surfactants are thosewhich are reasonably stable throughout a wide pH range. Surfactants aredescribed more fully, for example, in U.S. Pat. No. 3,959,458, toAgricola et al.; U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No.4,051,234, to Gieske et al, the disclosures of which are incorporatedherein by reference in their entireties.

The surfactant or mixtures of compatible surfactants that are includedin addition to the anionic surfactants can be present in thecompositions of the present disclosure in from 0.1% to 5.0%, in anotherembodiment from 0.3% to 3.0% and in another embodiment from 0.5% to 2.0%by weight of the total composition. These ranges do not include theanionic surfactant amounts.

In an embodiment, the compositions of the present disclosure include azwitterionic surfactant, for example a betaine surfactant, for examplecocamidopropylbetaine, e.g. in an amount of from 0.1% to 4.5% by weight,e.g. from 0.5 to 2% by weight cocamidopropylbetaine.

Tartar control agents: In various embodiments of the present disclosure,the compositions comprise an anticalculus (tartar control) agent.Suitable anticalculus agents include without limitation phosphates andpolyphosphates (for example pyrophosphates and tripolyphosphates),polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinccitrate trihydrate, polypeptides, polyolefin sulfonates, polyolefinphosphates, and diphosphonates. The compositions of the disclosure thusmay comprise phosphate salts in addition to the zinc phosphate. Inparticular embodiments, these salts are alkali phosphate salts, e.g.,salts of alkali metal hydroxides or alkaline earth hydroxides, forexample, sodium, potassium or calcium salts. “Phosphate” as used hereinencompasses orally acceptable mono- and polyphosphates, for example,P₁₋₆ phosphates, for example monomeric phosphates such as monobasic,dibasic or tribasic phosphate; and dimeric phosphates such aspyrophosphates; and multimeric phosphates, such as tripolyphosphates,tetraphosphates, hexaphosphates and hexametaphosphates (e.g., sodiumhexametaphosphate). In particular examples, the selected phosphate isselected from alkali dibasic phosphate and alkali pyrophosphate salts,e.g., selected from sodium phosphate dibasic, potassium phosphatedibasic, dicalcium phosphate dihydrate, calcium pyrophosphate,tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodiumtripolyphosphate, and mixtures of any of two or more of these. In aparticular embodiment, for example the compositions may comprisetetrasodium pyrophosphate in an amount of from 0.5 to 5% by weight,e.g., 1-3%, or 1-2% or about 2% by weight of the composition. In anotherembodiment, the compositions may comprise a mixture of tetrasodiumpyrophosphate (TSPP) and sodium tripolyphosphate (STPP), e.g., inproportions of TSPP at from 0.5 to 5 wt. %, such as from 1 to 2 wt. %and STPP at from 0.5% to 6 wt. %, such as 1 to 4%, or 2 to 3% by weightof the composition. Such phosphates are provided in an amount effectiveto reduce erosion of the enamel, to aid in cleaning the teeth, and/or toreduce tartar buildup on the teeth, for example in an amount of from 0.2to 20 wt. %, e.g., from 1 to 15 wt. %, by weight of the composition.

Flavoring Agents: The oral care compositions of the disclosure may alsoinclude a flavoring agent. Flavoring agents which are used in thepractice of the present disclosure include, but are not limited to,essential oils as well as various flavoring aldehydes, esters, alcohols,and similar materials. Examples of the essential oils include oils ofspearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus,marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful aresuch chemicals as menthol, carvone, and anethole. Certain embodimentsemploy the oils of peppermint and spearmint. The flavoring agent may beincorporated in the oral composition at a concentration of from 0.1 to5% by weight e.g., from 0.5 to 1.5% by weight.

Polymers: The oral care compositions of the disclosure may also includeadditional polymers to adjust the viscosity of the formulation orenhance the solubility of other ingredients. Such additional polymersinclude polyethylene glycols, polysaccharides (e.g., cellulosederivatives, for example carboxymethyl cellulose, microcrystallinecellulose or polysaccharide gums, for example xanthan gum or carrageenangum). Acidic polymers, for example polyacrylate gels, may be provided inthe form of their free acids or partially or fully neutralized watersoluble alkali metal (e.g., potassium and sodium) or ammonium salts. Inone embodiment, the oral care composition may contain PVP. PVP generallyrefers to a polymer containing vinylpyrrolidone (also referred to asN-vinylpyrrolidone, N-vinyl-2-pyrrolidione and N-vinyl-2-pyrrolidinone)as a monomeric unit. The monomeric unit consists of a polar imide group,four non-polar methylene groups and a non-polar methane group.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arabic, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of from 0.5% to5.0% by weight of the total composition are used.

The compositions of the disclosure may include an anionic polymer, forexample in an amount of from 0.05 to 5%. Examples of such agentsgenerally known for use in dentifrice are disclosed in U.S. Pat. Nos.5,188,821 and 5,192,531, both of which are incorporated herein byreference in their entirety; and include synthetic anionic polymericpolycarboxylates, such as 1:4 to 4:1 copolymers of maleic anhydride oracid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether/maleic anhydride having a molecular weight(M.W.) of from 30,000 to 1,000,000, such as from 300,000 to 800,000.These copolymers are available for example as Gantrez, e.g., AN 139(M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97 PharmaceuticalGrade (M.W. 700,000) available from ISP Technologies, Inc., Bound Brook,N.J. 08805. The enhancing agents when present are present in amountsranging from 0.05 to 3% by weight. Other operative polymers includethose such as the 1:1 copolymers of maleic anhydride with ethylacrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene,the latter being available for example as Monsanto EMA No. 1103, M.W.10,000 and EMA Grade 61, and 1:1 copolymers of acrylic acid with methylor hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinylether or N-vinyl-2-pyrrolidone. Suitable generally, are polymerizedolefinically or ethylenically unsaturated carboxylic acids containing anactivated carbon-to-carbon olefinic double bond and at least onecarboxyl group, that is, an acid containing an olefinic double bondwhich readily functions in polymerization because of its presence in themonomer molecule either in the alpha-beta position with respect to acarboxyl group or as part of a terminal methylene grouping. Illustrativeof such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic,crotonic, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic,beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic,glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic,2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids andanhydrides. Other different olefinic monomers copolymerizable with suchcarboxylic monomers include vinylacetate, vinyl chloride, dimethylmaleate and the like. Copolymers contain sufficient carboxylic saltgroups for water-solubility. A further class of polymeric agentsincludes a composition containing homopolymers of substitutedacrylamides and/or homopolymers of unsaturated sulfonic acids and saltsthereof, in particular where polymers are based on unsaturated sulfonicacids selected from acrylamidoalykane sulfonic acids such as2-acrylamide 2 methylpropane sulfonic acid having a molecular weight offrom 1,000 to 2,000,000. Another useful class of polymeric agentsincludes polyamino acids containing proportions of anionicsurface-active amino acids such as aspartic acid, glutamic acid andphosphoserine, e.g. as disclosed in U.S. Pat. No. 4,866,161, issued toSikes et al., which is also incorporated herein by reference in itsentirety.

Humectants: Within certain embodiments of the oral compositions, it isalso desirable to incorporate a humectant to prevent the compositionfrom hardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerin,sorbitol, xylitol, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment of the disclosure, theprincipal humectant is one of glycerin, sorbitol or a combinationthereof. The humectant may be present at levels of greater than 15 wt.%, such as from 15 wt. % to 55 wt. %, or from 20 wt. % to 50 wt. %, orfrom 20 wt. % to 40 wt. %, or about 20% or about 30% or about 40%, basedon the total weight of the composition.

Other optional ingredients: In addition to the above-describedcomponents, the embodiments of this disclosure can contain a variety ofoptional oral care ingredients some of which are described below.Optional ingredients include, for example, but are not limited to,adhesives, sudsing agents, flavoring agents, sweetening agents such assodium saccharin, additional antiplaque agents, abrasives, aestheticssuch as TiO₂ coated mica or other coloring agents, such as dyes and/orpigments.

In an embodiment, the compositions of the present disclosure can haveany pH suitable for in a product for use in oral care. Examples ofsuitable pH ranges are from 6 to 9, such as from 6.5 to 8.

In an embodiment, the oral care compositions of the present disclosureare either essentially free of or do not include any sodiumhexametaphosphate, such as is used in the compositions of U.S. Pat. No.3,095,356, the disclosure of which is incorporated herein by referencein its entirety. In an embodiment, the oral care compositions of thepresent disclosure are either essentially free of or do not include anyof a halogenated diphenyl ether, such as those recited in U.S. PatentApplication Publication No. 2013/0216485, the disclosure of which isincorporated herein by reference in its entirety. In an embodiment, theoral care compositions of the present disclosure are either essentiallyfree of or do not include any of TRPV1 activators and/or vanitrope, asused in the compositions taught in CA 2760445, the disclosure of whichis incorporated herein by reference in its entirety. In an embodiment,the oral care compositions of the present disclosure are eitheressentially free of or do not include any of a high intensity sweetenerselected from the group consisting of trichloro-sucrose (sucralose),acesulfame, neohesperidine DC, thaumatin, glycyrrhizin, mogroside IV,mogroside V, cyclocariosideI,N—[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine1-methyl ester,N—[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methyl-butyl]-L-α-aspartyl]-L-phenylalanine1-methyl ester,N—[N-[3-(3-methoxy-4-hydroxyphenyl)-propyl]-L-α-aspartyl]-L-phenylalanine1-methyl ester, and mixtures thereof. In an embodiment, the compositionsof the present disclosure are either essentially free of or do notinclude any of a high intensity sweetener having a 10% sucroseequivalence of from 500-600, as disclosed in U.S. Patent ApplicationPublication No. 2012/0082630, the disclosure of which is hereinincorporated by reference in its entirety. By “essentially free” ismeant that the compositions have no more than 0.01% by weight of thesecompounds.

In an embodiment, the compositions of the present disclosure are eitheressentially free of or do not include any complexing agents forincreasing solubility of zinc phosphate and/or for maintaining thestannous fluoride in solution. Examples of known complexing agents thatcan be excluded from the compositions of the present disclosure includethe chelating agents taught in U.S. Patent Application No. 2007/0025928,the disclosure of which is hereby incorporated by reference in itsentirety. Such chelating agents include mineral surface-active agents,including mineral surface-active agents that are polymeric and/orpolyelectrolytes and that are selected from phosphorylated polymers,wherein if the phosphorylated polymer is a polyphosphate, thepolyphosphate has average chain length of 3.5 or more, such as 4 ormore; polyphosphonates; polycarboxylates; carboxy-substituted polymers;copolymers of phosphate- or phosphonate-containing monomers or polymerswith ethylenically unsaturated monomers, amino acids, proteins,polypeptides, polysaccharides, poly(acrylate), poly(acrylamide),poly(methacrylate), poly(ethacrylate), poly(hydroxyalkylmethacrylate),poly(vinyl alcohol), poly(maleic anhydride), poly(maleate) poly(amide),poly(ethylene amine), poly(ethylene glycol), poly(propylene glycol),poly(vinyl acetate) and poly(vinyl benzyl chloride); and mixturesthereof. Other known complexing agents that can be excluded from thecompositions of the present disclosure include those taught in CA2634758, the disclosure of which is incorporated here by reference inits entirety. Examples include polyphosphorylated inositol compoundssuch as phytic acid, myo-inositol pentakis(dihydrogen phosphate);myo-inositol tetrakis(dihydrogen phosphate), myo-inositoltrikis(dihydrogen phosphate), and alkali metal, alkaline earth metal orammonium salts of any of the above inositol compounds. Phytic acid isalso known as myo-inositol 1,2,3,4,5,6-hexakis (dihydrogen phosphate) orinositol hexaphosphoric acid.

The present application further discloses methods of using thecompositions described herein to increase zinc levels in the enamel andto treat, reduce or control the incidence of enamel erosion. The methodscomprise applying any of the compositions as described herein to theteeth, e.g., by brushing, or otherwise administering the compositions tothe oral cavity of a subject in need thereof. The compositions can beadministered regularly, such as, for example, one or more times per day.In various embodiments, administering the compositions of the presentdisclosure to a patient can provide one or more of the followingbenefits: (i) reduce hypersensitivity of the teeth, (ii) reduce plaqueaccumulation, (iii) reduce or inhibit demineralization and promoteremineralization of the teeth, (iv) inhibit microbial biofilm formationin the oral cavity, (v) reduce or inhibit gingivitis, (vi) promotehealing of sores or cuts in the mouth, (vii) reduce levels of acidproducing bacteria, (viii) increase relative levels of non-cariogenicand/or non-plaque forming bacteria, (ix) reduce or inhibit formation ofdental caries, (x) reduce, repair or inhibit pre-carious lesions of theenamel, e.g., as detected by quantitative light-induced fluorescence(QLF) or electrical caries measurement (ECM), (xi) treat, relieve orreduce dry mouth, (xii) clean the teeth and oral cavity, (xiii) reduceerosion, (xiv) whiten teeth; (xv) reduce tartar build-up, and/or (xvi)promote systemic health, including cardiovascular health, e.g., byreducing potential for systemic infection via the oral tissues. Thedisclosure further provides compositions for use in any of the abovemethods. Further embodiments provide methods wherein at least one toothis remineralized after administration of a composition as describedherein.

Compositions according to the present invention can be made by themethods and procedures known to those skilled in the art.

The present application further discloses a method of making any of thecompositions of the present disclosure. The method comprises combiningzinc phosphate and stannous fluoride in water to form an aqueous zincphosphate mixture having a water concentration of 12% or more and a pHranging from 6 to 9, such as from 6.5 to 8. In some embodiments, thezinc phosphate is added to the dentifrice composition as a preformedsalt and remains essentially insoluble in the aqueous mixture. Theamount of water employed in the mixture can be any of the amountsrecited herein for the compositions of the present disclosure. Anystandard mixing techniques can be employed to combine the ingredientsand form a stable composition without the need for additional complexingagents to solubilize the stannous fluoride, such as any of the abovedisclosed complexing or chelating agents, or the use of anhydrous mixingtechniques such as dissolving stannous fluoride in an anhydrous materialsuch as glycerin.

EXAMPLES Example 1—Dentifrice Formulation

Test dentifrice comprising 1% zinc phosphate and 0.454% stannousfluoride is prepared in accordance with the following formulation ofTable 1. Ingredients are listed by weight of the composition.

TABLE 1 Ingredient Wt. % Water Q.S. (e.g., 15-40) Thickener 0.5-5 (e.g.3.6) Humectants 15-55 (e.g. 48) Tartar Control Agents 0.5-5 (e.g. 2)Abrasives 10-30 (e.g. 20) Stannous fluoride 0.05-11 (e.g. 0.454) Minors(flavor, color) 0.5-5 (e.g. 2.25) Surfactants 0.1-15 (e.g. 2.75) ZincPhosphate 0.05-5 (e.g. 1 or 2)

Example 2—Stability Data

Three separate dentifrice samples of a formulation similar to theformulation shown in Table 1 (above) are made. The three samples areheld at three different temperatures: room temperature (approximately25° C.), approximately 40° C. and approximately 49° C., for a period ofthree months. The initial fluoride concentration for each sample ismeasured at the beginning of the study and is then periodically measuredafter each month of the study. The results show that in the presence ofzinc phosphate, fluoride concentrations remain sufficiently stable atall three temperatures for a period of three months.

The data shows that by simply combining stannous fluoride and zincphosphate, a stable formulation can be achieved that provides goodanti-microbial benefits without the need for employing techniquestypically used for stabilizing stannous fluoride compositions in water.

Example 3

An Example 3 dentifrice is made by adding 0.454% by weight stannousfluoride to a commercially available toothpaste. As a first controlsample, a commercially available toothpaste without stannous fluoride isused. Both the Example 3 toothpaste and the first control sample have azinc phosphate concentration of 1% by weight. Another commerciallyavailable fluoride toothpaste, which includes 1100 ppm (mass fraction)fluoride and 1 wt % zinc citrate, is used as a second control sample.

An in vitro methodology is used to determine the enamel protectionactivity of the formulation prototype of Example 3. Enamel substrates(N=6/8 per cell) are prepared by embedding bovine incisors in amethacrylate-based resin and polishing with 600 and 1200 grit carbidepaper consecutively. Care is taken not to penetrate the dentin layerwhile polishing the enamel to a mirror finish. Prior to testing, allenamel substrates are pre-etched with 5% citric acid for 30 seconds.Half the side of each substrate is masked with acid resistant tape toprotect the surface as control surface. The model used to evaluate theproducts alternated 1-min product treatment periods with 2-min acidexposure periods according to the daily sequence of T-C-C-C-C-T(T=product treatment, C=acid challenge). The acid challenge is performedwith a 1% aqueous solution of citric acid (unbuffered) adjusted topH=3.8 with NaOH. All enamel substrates are kept in a sterile artificialsaliva solution at 37° C. while not undergoing treatment or challenge.This regimen is conducted for a total of five days, at the end of whicha microhardness analysis is used to quantify the amount of enamel lostdue to erosion on each enamel substrate on the protected and exposedsurface. The change in percentage hardness is calculated. Withouttreatment, using deionized water in place of test dentifrice, the changein percentage hardness is very high, ca. 80%, with slight variation fromexperiment to experiment depending on the particular substrate.

The dentifrice of Example 3 and both control samples are tested usingthe above procedure. The Example 3 formula containing both zincphosphate and stannous fluoride is effective against demineralization inthis in vitro pH-cycling model designed to investigate the protectiveeffect of treatments on early enamel dissolution, with an averagereduction in hardness following repeated acid challenges of only about89.4 g_(f)·mm⁻². This is greater than the average 83.32 g_(f)·mm⁻²reduction in hardness seen for the first control sample using zincphosphate without stannous fluoride, but is still significantly betterthan the results for the second control sample, which gave an averagereduction in hardness of about 98.5 g_(f)·mm⁻². Hardness here isdetermined by the Knoop Hardness HK test. Thus the enamel protectionactivity of the zinc phosphate and stannous fluoride formulation ofExample 3 is considered to be excellent.

Example 4

A demineralization/remineralization study of two commercial comparativecompositions (Comp. Ex. I and II) and an exemplary composition of thepresent invention (Example 4) is conducted on bovine teeth. Theformulations of Comparative Ex. I and Example 4 are provided below inTable 2. Comparative Example II is a commercial sodium fluoridetoothpaste which contains no zinc or stannous agents.

TABLE 2 Ingredient % w/w Example 4 Comp. Ex. I Water and minors 11.749.50 (color, flavor) Stannous fluoride 0.454 0.454 Zinc lactate — 2.50Zinc phosphate 1.15 — Thickeners 2.9 3.15 Glycerin 40.79 34.65 Abrasivesilica 24.00 20.00 Sodium — 13.00 Hexametaphosphate Propylene Glycol4.00 7.00 Trisodium Citrate 3.00 — Dihydrate Sodium 3.00 —Tripolyphosphate Polyethylene Glycol 3.00 7.00 600 Tetrasodium 2.00 —Pyrophosphate Anionic Surfactant 1.75 1.00 Trisodium Phosphate — 1.10Zwitterionic 1.00 — Surfactant Sodium Gluconate — 0.65 Anionic Polymer0.61 — Citric Acid 0.60 —

Bovine teeth are soaked in heated saliva overnight to form a pellicle.The teeth are then treated twice a day for ten (10) days with a 1:2toothpaste:water slurry and subjected to two minute acid challenges witha 1% citric acid solution.

As illustrated by the data described in Table 3 (below), only theexemplary composition of the present disclosure demonstrates an abilityto actually remineralize enamel, while the comparative examples couldnot deliver the same benefit.

TABLE 3 Composition % Mineral Loss Example 4 (−) 4.07 Comp. Ex. I 53.12Comp. Ex. 71.29

Example 5

A 13-week stability study is performed with two arms, one at roomtemperature and one at 40° C. Formulation A-1 is a dentifrice containing0.454% stannous fluoride, 1% zinc phosphate, 1.2% citrate buffer, and 4%TSPP. Formulation B contains 0.454% stannous fluoride, 1% zinc oxide,1.2% citrate buffer, and 4% TSPP. The results are shown in Table 4below.

TABLE 4 Soluble Fluoride (ppm) Soluble Tin (wt %) Soluble Zinc (wt %) 8weeks 13 Weeks 8 weeks 13 Weeks 8 weeks 13 Weeks Initial RT 40° C.Initial RT 40° C. Initial RT 40° C. Form. A-1 1099 1080 1011 0.27 0.260.20 0.33 0.36 0.29 Form. B 1124 1138 1136 0.07 0.00 0.00 0.44 0.32 0.22

The results demonstrate that while the use of zinc oxide results incomparable fluoride stability to using zinc phosphate, the solublestannous level and soluble zine level is significantly reduced bothinitially and over the course of the study when zinc oxide is usedinstead of zinc phosphate. This demonstrates that zinc phosphate has theability to stabilize stannous ion against oxidative degradation, whereaszinc oxide does not. Without being bound by theory, it is believed thatzinc oxide when solubilized can adversely interact with stannousfluoride to cause conversion of the stannous ion to stannous hydroxide,which precipitates out. In contrast, zinc phosphate is able to maintainzinc and stannous in a bioavailable soluble form.

Example 6

An additional stability study is performed in which the soluble tinrecoverable is compared between a formulation according to the presentinvention (Formulation A-2) and two commercial competitors (ComparativeB and C). The study is performed for 13 weeks at room temperature.Formulation A-2 comprises 0.454% stannous fluoride, 1% zinc phosphate,1.2% citrate buffer, and 2% TSPP (Formula A-2 is essentially the same asFormulation A-1, except that it contains 2% TSPP instead of 4% TSPP).Comparative composition B is a low water composition comprising 0.454%stannous fluoride, about 2.5% zinc lactate, and about 10% water.Comparative composition C is a high-water composition comprising 0.454%stannous fluoride, 0.27% stannous chloride, 0.5% zinc citrate, and about43% water. The results shown in Table 5 below demonstrate that whileexisting low-water stannous fluoride compositions can achieve stannousion stability, high water compositions cannot. Indeed, the commercialformulation comprising more than double the total tin salt contentresults in half as much recoverable soluble tin at the conclusion of thestudy.

TABLE 5 Total Added Soluble Tin at 13 Tin (wt %) Weeks (wt %)Formulation A-2 0.34 0.22 Comparative B 0.34 0.20 (low water)Comparative C 0.72 0.10 (high water)

Example 7

Tin can exist in two oxidation states, Sn(II) (stannous) and Sn(IV)(stannic). Oxidizing agents, including atmospheric oxygen, can oxidizeSn(II) to Sn(IV). Soluble Sn(II) can be rapidly quantified by titratingwith the inorganic oxidizing agent iodine, such as according to themethod of Howe, P., and Watts, P., Tin and inorganic tin compounds,(World Health Organization, 2005). Formulation A-2, and ComparativeFormulations B and C, as described above, are tested for soluble tinusing this method. The results are shown in Table 6 below. These resultsfurther demonstrate that a composition according to the inventionunexpectedly stabilizes tin in a high water composition.

TABLE 6 Tin (II) (Wt %) Formulation A-2 0.25 Comparative B (low 0.13water) Comparative C (high 0.16 water)

Example 8

The antibacterial efficacy of Formulation A-2 is compared to variouscommercial competitor formulations using the planktonic bacteria ATPluminescence assay described in Example 3. Formulation A-2 is adentifrice comprising 0.454% stannous fluoride, 1% zinc phosphate, 1.2%citrate buffer, and 2% TSPP. Comparative composition C is a high-watercomposition comprising 0.454% stannous fluoride, 0.27% stannouschloride, 0.5% zinc citrate, and about 43% water. ComparativeComposition D is a commercial stabilized stannous dentifrice comprisingabout 0.45% stannous fluoride in a substantially anhydrous (zero-water)base. The results are shown in Table 7 below. Samples are diluted 1:8 ina mixture of saliva and PBS. Positive controls are measured for salivaalone and the saliva/PBS mixture used for sample dilution. The resultsshow that Formulation A-2 is significantly more effective in killingbacteria compared to any of the commercial competitors.

TABLE 7 Luminescence (cps) Saliva (Control) 168398 Saliva/PBS 109810(Control) Formulation A-2  4954 Comparative C 65192 (high water)Comparative D 11612 (no water)

While the present invention has been described with reference toembodiments, it will be understood by those skilled in the art thatvarious modifications and variations may be made therein withoutdeparting from the scope of the present invention as defined by theappended claims.

1-17. (canceled)
 18. A method of treating or reducing bacterialcolonization and biofilm development in the oral cavity in a subject inneed thereof, wherein the method comprises administering an oral carecomposition comprising: an orally acceptable carrier; zinc phosphate;stannous fluoride; and wherein the oral care composition is administeredto the oral cavity of the subject in need thereof.
 19. The method ofclaim 18, wherein the zinc phosphate is a preformed salt of zincphosphate.
 20. The method of claim 18, wherein zinc phosphate is presentin an amount sufficient so that the stannous fluoride dissociates toprovide a therapeutically effective amount of stannous ions in aqueoussolution.
 21. The method of claim 18, wherein the amount of zincphosphate is from 0.05 to 5% by weight, relative to the weight of theoral care composition.
 22. The method of claim 18, wherein the amount ofthe stannous fluoride is from 0.05% to 5% by weight, relative to theweight of the oral care composition.
 23. The method of claim 18, whereinthe amount of the water is about 12% by weight or more, relative to theweight of the oral care composition.
 24. The method of claim 18, whereinthe oral care composition further comprises an abrasive.
 25. The methodof claim 18, further comprising one or more humectants and/or one ormore surfactants.
 26. The method of claim 18, further comprising aneffective amount of one or more alkali phosphate salts.
 27. The methodof claim 18, further comprising a whitening agent.
 28. The method ofclaim 18, further comprising one or more sources of zinc ions inaddition to the zinc phosphate.
 29. The method of claim 18, wherein theoral care composition is a dentifrice, powder, cream, strip or gum. 30.The method of claim 18, wherein the oral care composition comprises:from 0.5 to 3% by weight zinc phosphate; from 0.05 to 11% by weightstannous fluoride; from 1 to 8% by weight alkali phosphate saltsselected from sodium phosphate dibasic, potassium phosphate dibasic,dicalcium phosphate dihydrate, tetrasodium pyrophosphate, tetrapotassiumpyrophosphate, calcium pyrophosphate, sodium tripolyphosphate, andmixtures of any two or more of these, relative to the weight of the oralcare composition; and a silica abrasive.
 31. The method of claim 18,wherein the oral care composition is a gel.
 32. The method of claim 18,wherein the pH of the oral care composition is less than
 7. 33. Themethod of claim 18, wherein the amount of zinc phosphate in the oralcare composition is from 0.9 to 1.1% by weight, relative to the weightof the oral care composition, and wherein the amount of stannousfluoride is from 0.4 to 0.5% by weight, relative to the weight of theoral care composition.